AUTHOR=Kepplinger Bernhard , Wen Xin , Tyler Andrew Robert , Kim Byung-Yong , Brown James , Banks Peter , Dashti Yousef , Mackenzie Eilidh Sohini , Wills Corinne , Kawai Yoshikazu , Waldron Kevin John , Allenby Nicholas Edward Ellis , Wu Ling Juan , Hall Michael John , Errington Jeff 

TITLE=Mirubactin C rescues the lethal effect of cell wall biosynthesis mutations in Bacillus subtilis

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1004737

DOI=10.3389/fmicb.2022.1004737

ISSN=1664-302X

ABSTRACT=Growth of most rod-shaped bacteria is accompanied by the insertion of new peptidoglycan into the cylindrical cell wall. This insertion, which helps maintain and determine the shape of the cell, is guided by a protein machine called the rod complex or elongasome. Although most of the proteins in this complex are essential under normal growth conditions, cell viability can be rescued, for reasons that are not understood, by the presence of a high (mM) Mg2+ concentration. We screened for natural product compounds that could rescue the growth of mutants affected in rod-complex function. By screening >2,000 extracts from a diverse collection of actinobacteria, we identified the compound, mirubactin C, related to the known iron siderophore mirubactin A, which rescued growth in the low micromolar range, and this activity was confirmed by synthesising mirubactin C. The compound also displayed toxicity at higher concentrations, and this effect appears related to iron homeostasis. However, several lines of evidence suggest that the mirubactin C rescuing activity is not due simply to iron sequestration. The results demonstrate a novel antibacterial compound and add to growing evidence that bacterial siderophores have a range of activities beyond simple iron acquisition.